Neurodegenerative proteinopathies are characterized by degeneration attributed to abnormal pathogenic aggregates. Proteinopathies can be linked to specific genetic variants and resulting amino-acid modifications within aggregating proteins; however, can occur in the absence of a known mutation. Pharmaceuticals have found limited success, and without regenerative treatments, individuals in late stages of diseases will unlikely improve. To identify potential strategies to treat proteinopathies and mechanisms behind their development, we investigated the utility of the axolotl (Ambystoma mexicanum). The human CNS possesses cells that contribute to natural turnover; however, these cells are largely unreactive to damage. In contrast, the axolotl salamander can regenerate damaged or excised complex anatomical structures, including portions of the brain. Axolotl neurogenesis occurs continually and extensively in response to injury, regenerating healthy and functionally diverse cell types. With the recent sequencing of the complete axolotl genome, it is now possible to determine the genetic capacity of axolotls to develop neurodegenerative disease. Towards this goal, we have performed structural comparison of proteins implicated in human neurodegenerative proteinopathies to the homologous axolotl proteins to provide insight into future experiments aimed at characterizing innate axolotl neuroresilience or neuroregeneration.